Project Summary/Abstract Physical Sciences Inc. (PSI), in collaboration with Joslin Diabetes Center (JDC), proposes to develop a non-invasive high-resolution retinal oximetry platform that is able to monitor in vivo retinal oxygen saturation (SpO2) in the rodent eye down to the capillary level. Capillary level assessment is needed to study the early onset of disease. This oximetry imaging feature will be built on an existing PSI's Multi-modal Adaptive Optics Small-animal Imager (MAOSI), which allows high-resolution (<1m transverse resolution, <5m axial resolution) investigation of retinal microvasculature. Simultaneous, co-scanning adaptive optics scanning laser ophthalmoscopy / optical coherent tomography (AOSLO/AOOCT) rasters will provide significant benefits for image guidance, cross-modal registration and averaging. With proper management of light safety levels set by ANSI Z136.1 ? 2014 with special consideration of rodent eyes' geometry, the proposed project will take advantage of the high molar extinction coefficient of oxy-hemoglobin and deoxy- hemoglobin within the blue region of the light spectrum to enhance SpO2 detection sensitivity. In addition, the project will incorporate a state-of-the-art split-detector AOSLO imaging modality with custom designed multi-aperture fibers that is ideally matched with rodent eye numerical aperture to efficiently collect multiply scattered photons through vessels (rather than reflection from vessel), allowing the measurement of true light transmittance from blood. An intuitive graphic user interface will be designed and developed to robustly control all the imaging subsystems and provide image post-processing tools for oximetry analysis. A temperature controlled holder will keep the animal body temperature constant and minimize cornea and lens opacifications. After fully constructed and tested, the instrument will be moved to JDC for oximetry measurement on normal and diabetic animals. Based on the Phase I results and conclusions, a second- generation upgraded oximetry MAOSI system will be developed in Phase II to enable oximetry on different animal species/strains/diseases, providing an important cutting-edge metabolic imaging tool for research institutes and pharmaceutical companies.